Class III antiarrhythmic agents may be categorized as having the ability to markedly prolong dog Purkinje fiber action potential duration without producing significant changes in maximal upstroke velocity. Unlike Class I anit-arrhythmic agents, a pure Class III agent displays no effect on cardiac sodium channels. The electrophysiologic properties of a compound defining a Class III activity profile are observed in vivo as negligible effects on atrial, ventricular and H-V conduction lines while producing a marked increase (greater than 20 percent) in both the atrial and ventricular refractory period. In contrast, Class I agents will demonstrate a marked slowing of ventricular conduction velocity, generally without significant changes in the refractory period. Recent reviews of these agents are by: Bexton et al., Pharmac. Ther., 17, 315-55 (1982); Vaughan-Williams, J. Clin. Pharmacol., 24, 129-47 (1984); and Steinberg et al., Ann. Rep. Med. Chem., 21, 95-108 (1986).
The following workers have reported the selective Class III antiarrhythmic activity of the dextro enantiomer of 4-(2-isopropylamino-1-hydroxyethyl)-methanesulfonamide (MJ-1999, Sotalol): Taggart et al., Clin. Sci., 69, 631-636 (1985) and McComb et al., J. Am. Coll. Cardiol., 5, 438 (1985).
Wohl et al., disclose N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino]-benzamide hydrochloride as a potential class III antiarrhythmic agent in U.S. Pat. No. 4,544,654, Oct. 1, 1985.
Cross et al., have recently reported various N-heterocycle methyl substituted .alpha.-phenylethylamine derivatives as useful antiarrhythmic agents in European Patent 0281254, Sept. 7, 1988, as well as other alkyl-sulfonamide compounds reported in European Patent 0286277 and European Patent 0286278, Oct. 12, 1988. Almgren et al. have recently reported 4-cyano-phenyl ether derivatives as useful antiarrhythmic agents in European Patent 0322390, June 28, 1989.